الفهرس 
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Abstract
HCC is reported to be a very common type of cancer. Most of the patients are lately diagnosed. Approaches on antioxidant, anti-fibrotic and anti-inflammatory effects are considered to be the most effective strategies to lower the mortality rate and the morbidity of HCC.
Induction of cancer could be done by different ways; one of these ways is the induction of hepatic carcinogenesis by TCA in a dose of (500 mg/kg/day) for 5 days.
Long ago, plant extracts are frequently used in treatment of various illnesses; So that the current study aimed to study thymol as one of the herbal extracts, also DIA was previously reported to be effective in breast cancer as it reduced proliferation and stimulated apoptosis and to inhibit EB-induced pathological changes.
The present study explained the effect of DIA and thymol in the treatment of pre-neoplastic lesion mediated by TCA in comparison to 5-FU as a standard anti-cancer in treatment of HCC; focusing on their inhibitory effect on IL-1β, HIF-1-α , VEGF or on p-AKT pathways, and that inhibition resulted in induction of apoptosis.
Serum liver enzymes, oxidative stress parameters, inflammatory parameter (IL-1 β), and angiogenesis marker vascular endothelial growth factor (VEGF) were assessed along with histopathological evaluation. An apoptotic marker as caspase-3 expression was measured by western blotting. Immunoexpression of proliferating cell nuclear antigen (PCNA) and hypoxia-inducible factor-1α (HIF-1α) was evaluated.
The current study showed that induction of hepatic dysplasia was evidenced by histo-pathological changes. Such changes were accompanied with significant elevations of the liver enzyme ALT, immuno-histochemical expression of PCNA, hepatic IL-1 β, HIF-1α, VEGF, and oxidative stress markers, as well as by a significant decrease in the apoptotic marker (caspase-3). Rats received DIA and/or thymol revealed improvement of hepatic dysplasia as well as amelioration of the associated biochemical and immune-histochemical parameters.
These results in comparison to 5-FU revealed more improvement than 5-FU at the level of liver function, histopathological findings, ani-oxidant and anti-inflammatory effect, as well as apoptosis; so that further researches needed to study other pathways involved in the mechanisms of action of thymol and DIA.
Conclusion
Thymol and DIA could ameliorate TCA induced dysplasia either by inhibition of oxidative stress thus inhibiting phosphorylated AKT resulting in induction of apoptosis, or by inhibition of IL-1β, HIF-1α resulting in inhibition of VEGF and suppression of angiogenesis.